Lactose Permease

Function of Lactose Permease
Lactose Permease (PDB entry 1pv7) is a transmembrane protein that facilitates the passage of lactose across the phospholipid bi-layer of the cell membrane. The transport mechanism used is an active co-transport that uses the inwardly directed H+ electrochemical gradient as its driving force. As a result, the lactose is accompanied from the periplasm to the cytoplasm of the cell by an H+ proton.

Lactose is a disaccharide carbohydrate found primarily in mammalian milk. The disaccharide consists of the monosacharides glucose and galactose. When the lactose is ingested and absorbed into the cell, the enzyme lactase breaks the disaccharide into its monosaccharide subunits. These are in turn used in the cellular respiration process and broken down further into energy for the cell.

Lactose permease belongs to the family of so called Major Facilitators.

Structure of Lactose Permease
 Lactose permease is a transmembrane protein consisting of N- and C- terminal domains (depicted in this model by the blue and red hemispheres), each with six transmembrane helices symmetrically positioned within the permease. There are six sidechains that play an irreplaceable role in the active transport of lactose through the protein. Three of these sidechains, Glutamic Acid 126, Arginine 144 , and Glutamic Acid 269 have been shown to be crucial in substrate binding activities. Arginine 302, Histidine 322 , and Glutamic Acid 325 are known to play a significant role in proton translocation(moving the H+ proton) throughout the transport process. Additionally, there are two residues that are suspected to play an important role in the alignment of the galactopyranosyl end of the substrate. These are Cysteine 148 and Tryptophan 151.

These sidechains, which make up the active site of the protein, can be found within the large internal hydrophilic cavity of the lactose permease. It is here where the substrate is recieved for transport and it is the location from which it is deposited into the cell. The currently crystalized form of the permease is considered an 'inward-facing' conformation. This implies that the hydrophilic cavity mentioned previously is positioned with the opening towards the cytoplasm of the cell. Conversely, and outward-facing conformation would have the cavity facing the periplasm.

3D structures of lactose permease
2v8n - EcLACY – Escherichia coli

2cfp, 2cfq, 1pv6 - EcLACY (mutant)

2y5y – EcLACY (mutant) + affinity activator

1pv7 - EcLACY (mutant) + thiodigalactoside

Fucose permease
3o7q - EcFUCP

3o7p - EcFUCP (mutant)

Additional Resources
For additional information, see: Membrane Channels & Pumps

MSOE Center for BioMolecular Modeling


The physical models shown on this page were designed and built by the MSOE Center for BioMolecular Modeling. For more information about physical protein modeling, visit the CBM web site at http://cbm.msoe.edu/.